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JP2016027019A - Process for producing fused heterocyclic compound - Google Patents

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JP2016027019A
JP2016027019A JP2015124500A JP2015124500A JP2016027019A JP 2016027019 A JP2016027019 A JP 2016027019A JP 2015124500 A JP2015124500 A JP 2015124500A JP 2015124500 A JP2015124500 A JP 2015124500A JP 2016027019 A JP2016027019 A JP 2016027019A
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JP6432452B2 (en
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宮本　隆史
Takashi Miyamoto
隆史 宮本
大輔 笹山
Daisuke Sasayama
大輔 笹山
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Sumitomo Chemical Co Ltd
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    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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    • B29C45/28—Closure devices therefor
    • B29C45/2806—Closure devices therefor consisting of needle valve systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C45/00—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor
    • B29C45/17—Component parts, details or accessories; Auxiliary operations
    • B29C45/26—Moulds
    • B29C45/27—Sprue channels ; Runner channels or runner nozzles
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides

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Abstract

PROBLEM TO BE SOLVED: To provide an excellent method for producing a fused heterocyclic compound.SOLUTION: The present invention provides a method for producing a compound represented by formula (4) through a step B of making an acid chloride compound react with an amine compound to produce a compound represented by formula (3) or acid salt thereof; and a step C of cyclizing the compound represented by formula (3) or acid salt thereof in the presence of an acid at 100°C-180°C to obtain a compound represented by formula (4).SELECTED DRAWING: None

Description

本発明は、縮合複素環化合物の製造方法に関する。   The present invention relates to a method for producing a fused heterocyclic compound.

特許文献１には、２−（３−エチルスルファニルピリジン−２−イル）−５−トリフルオロメチルベンズオキサゾール等が有害生物に対して優れた防除効力を有することが記載されており、製造法２には、アミノフェノールとピリジンカルボン酸クロリドとを反応させてアミド体を合成し、該アミド体を閉環して合成する方法が記載されている。
また、非特許文献１には、イソニコチン酸カリウム塩が塩化オキサリルと反応してイソニコチン酸クロリドを製造する方法が記載されている。 Patent Document 1 describes that 2- (3-ethylsulfanylpyridin-2-yl) -5-trifluoromethylbenzoxazole and the like have an excellent control effect against pests, and production method 2 Describes a method in which an aminophenol and pyridinecarboxylic acid chloride are reacted to synthesize an amide, and the amide is cyclized.
Non-Patent Document 1 describes a method for producing isonicotinic acid chloride by reacting isonicotinic acid potassium salt with oxalyl chloride.

国際公開第２０１３／０１８９２８号International Publication No. 2013/018928

Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ（１９８６）， ２９， ８６０Journal of Medicinal Chemistry (1986), 29, 860

本発明は、式（４）

Figure 2016027019
［式中、
Ｒ1はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、
Ｒはそれぞれ独立して、ハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基、又はハロゲン原子を表し、
Ｒ5はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、
Ａ1は窒素原子又は＝ＣＨ−を表し、
ｍは１又は２を表し、
ｎは０、１、２又は３を表す］
で表される化合物の製造方法を提供することを課題とする。 The present invention relates to formula (4)
Figure 2016027019
[Where:
R 1 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom,
Each R independently represents a C1-C6 chain hydrocarbon group which may have a halogen atom, or a halogen atom;
R 5 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom,
A 1 represents a nitrogen atom or = CH-,
m represents 1 or 2,
n represents 0, 1, 2 or 3]
It aims at providing the manufacturing method of the compound represented by these.

本発明者等は、式（４）で表される化合物の製造方法を見出すべく検討した結果、本発明に至った。
即ち、本発明は以下の通りである。
〔１〕 式（２）

Figure 2016027019
［式中、Ｒ1はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、
Ｒはそれぞれ独立して、ハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基、又はハロゲン原子を表し、ｎは０、１、２または３を表し、Ｍはナトリウム、カリウム、又はリチウムを表す］で表される化合物と、塩化チオニルとを反応させて、式（１）
Figure 2016027019
［式中、Ｒ1、Ｒおよびｎは前記と同じ意味を表す。］
で表される化合物を得る工程Ａ（以下、工程Ａとも記す）；及び
式（１）で表される化合物と式（５）
Figure 2016027019
［式中、Ａ1は窒素原子又は＝ＣＨ−を表し、
Ｒ5はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、ｍは１または２を表す］
で表される化合物とを反応させることにより、式（３）
Figure 2016027019
［式中、Ｒ1、Ｒ、Ｒ5、Ａ1、ｍおよびｎは、前記と同じ意味を表す。］
で表される化合物またはその酸塩を製造する工程Ｂ（以下、工程Ｂとも記す）；及び
式（３）で表される化合物またはその酸塩を、酸の存在下で１００℃〜１８０℃で環化することにより、式（４）
Figure 2016027019
［式中、Ｒ1、Ｒ、Ｒ5、Ａ1、ｍおよびｎは、前記と同じ意味を表す。］
で表される化合物を得る工程Ｃ（以下、工程Ｃとも記す）；を含む、式（４）で表される化合物の製造方法。
〔２〕 工程Ｃにおける酸が、スルホン酸化合物である、〔１〕に記載の製造方法。
〔３〕 工程Ｃにおける酸が、ｐ−トルエンスルホン酸である、〔１〕に記載の製造方法。
〔４〕 工程Ｃにおける酸が、メタンスルホン酸である、〔１〕に記載の製造方法。
〔５〕 式（２）
Figure 2016027019
［式中、Ｒ1はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、
Ｒはそれぞれ独立して、ハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基、又はハロゲン原子を表し、ｎは０、１、２または３を表し、Ｍはナトリウム、カリウム、又はリチウムを表す］で表される化合物と、塩化チオニルとを反応させて、式（１）
Figure 2016027019
［式中、Ｒ1、Ｒおよびｎは前記と同じ意味を表す。］
で表される化合物を得る工程Ａ；及び
式（１）で表される化合物と式（５）
Figure 2016027019
［式中、Ａ1は窒素原子又は＝ＣＨ−を表し、
Ｒ5はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、ｍは１または２を表す］
で表される化合物とを反応させることにより、式（３）
Figure 2016027019
［式中、Ｒ1、Ｒ、Ｒ5、Ａ1、ｍおよびｎは、前記と同じ意味を表す。］
で表される化合物を製造する工程Ｂ；を含む、式（３）で表される化合物またはその酸塩の製造方法。
〔６〕 工程Ｂにおいて、用いる溶媒がエーテル溶媒を含む、〔１〕〜〔５〕いずれかに記載の製造方法。
〔７〕 式（２）
Figure 2016027019
［式中、Ｒ1はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、
Ｒはそれぞれ独立して、ハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基、又はハロゲン原子を表し、ｎは０、１、２または３を表し、Ｍはナトリウム、カリウム、又はリチウムを表す］で表される化合物と、塩化チオニルとを反応させて、式（１）
Figure 2016027019
［式中、Ｒ1、Ｒ及びｎは前記と同じ意味を表す。］
で表される化合物を得る工程Ａ；を含む、式（１）で表される化合物の製造方法。 As a result of investigations to find out a method for producing the compound represented by the formula (4), the present inventors have reached the present invention.
That is, the present invention is as follows.
[1] Formula (2)
Figure 2016027019
[In the formula, R 1 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom. Represent,
R independently represents a C 1-6 chain hydrocarbon group which may have a halogen atom, or a halogen atom, n represents 0, 1, 2 or 3, M represents sodium, A compound represented by formula (1) is reacted with thionyl chloride.
Figure 2016027019
[Wherein R 1 , R and n represent the same meaning as described above. ]
Step A to obtain a compound represented by formula (hereinafter also referred to as step A); and a compound represented by formula (1) and formula (5)
Figure 2016027019
[In the formula, A1 represents a nitrogen atom or = CH-;
R 5 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom; Represents 1 or 2]
Is reacted with a compound represented by the formula (3)
Figure 2016027019
[Wherein, R 1 , R, R 5 , A 1 , m and n represent the same meaning as described above. ]
Step B (hereinafter also referred to as Step B) for producing a compound represented by the formula: or a salt thereof; and a compound represented by the formula (3) or a salt thereof at 100 ° C. to 180 ° C. in the presence of an acid: By cyclization, formula (4)
Figure 2016027019
[Wherein, R 1 , R, R 5 , A 1 , m and n represent the same meaning as described above. ]
A process for producing a compound represented by formula (4), comprising: Step C (hereinafter also referred to as Step C);
[2] The production method according to [1], wherein the acid in Step C is a sulfonic acid compound.
[3] The production method according to [1], wherein the acid in Step C is p-toluenesulfonic acid.
[4] The production method according to [1], wherein the acid in Step C is methanesulfonic acid.
[5] Formula (2)
Figure 2016027019
[In the formula, R 1 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom. Represent,
R independently represents a C 1-6 chain hydrocarbon group which may have a halogen atom, or a halogen atom, n represents 0, 1, 2 or 3, M represents sodium, A compound represented by formula (1) is reacted with thionyl chloride.
Figure 2016027019
[Wherein R 1 , R and n represent the same meaning as described above. ]
Step A to obtain a compound represented by formula: and a compound represented by formula (1) and formula (5)
Figure 2016027019
[Wherein A 1 represents a nitrogen atom or ═CH—,
R 5 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom; Represents 1 or 2]
Is reacted with a compound represented by the formula (3)
Figure 2016027019
[Wherein, R 1 , R, R 5 , A 1 , m and n represent the same meaning as described above. ]
A process for producing a compound represented by formula (3) or a salt thereof:
[6] The production method according to any one of [1] to [5], wherein the solvent used in Step B includes an ether solvent.
[7] Formula (2)
Figure 2016027019
[In the formula, R 1 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom. Represent,
R independently represents a C 1-6 chain hydrocarbon group which may have a halogen atom, or a halogen atom, n represents 0, 1, 2 or 3, M represents sodium, A compound represented by formula (1) is reacted with thionyl chloride.
Figure 2016027019
[Wherein R 1 , R and n represent the same meaning as described above. ]
A process for producing a compound represented by the formula (1), which comprises the step A of obtaining a compound represented by the formula:

本発明により、式（４）で表される化合物を製造することができる。   According to the present invention, a compound represented by the formula (4) can be produced.

次に、本発明について説明する。   Next, the present invention will be described.

式（１）で表される化合物、式（３）で表される化合物および、式（４）で表される化合物は、例えば、以下の製造法により製造することができる。   The compound represented by Formula (1), the compound represented by Formula (3), and the compound represented by Formula (4) can be produced, for example, by the following production method.

本発明において、ハロゲン原子とは、フッ素原子、塩素原子、臭素原子及びヨウ素原子を表す。
本発明において、炭素数１〜６の鎖式炭化水素基とは、メチル基、エチル基、プロピル基、イソプロピル基、ヘキシル基等の炭素数１〜６のアルキル基；
ビニル基、１−プロペニル基、２−プロペニル基、１−ヘキセニル基等の炭素数１〜６のアルケニル基；
及びエチニル基、プロパルギル基、１−ペンチニル基、１−ヘキシニル基等の炭素数１〜６のアルキニル基を表す。
本発明において、ハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基としては、例えばメチル基、エチル基、イソプロピル基、ブチル基、ｔｅｒｔ−ブチル基、ヘキシル基、フルオロメチル基、クロロメチル基、ブロモメチル基、ヨードメチル基、ジフルオロメチル基、ジクロロメチル基、トリフルオロメチル基、トリクロロメチル基、２−フルオロエチル基、２−クロロエチル基、２，２−ジフルオロエチル基、２，２，２−トリフルオロエチル基、ペンタフルオロエチル基、ヘプタフルオロプロピル基等の、ハロゲン原子を有していてもよいＣ１−Ｃ６アルキル基；
ビニル基、２−プロペニル基、１−メチルビニル基、２−メチル−１−プロペニル基、３−ブテニル基、１−ヘキセニル基、１，１−ジフルオロアリル基、及びペンタフルオロアリル基等の、ハロゲン原子を有していてもよいＣ２−Ｃ６アルケニル基；
及びエチニル基、プロパルギル基、３−ブチニル基、１−ヘキシニル基、及び４，４，４−トリフルオロ−２−ブチニル基等の、ハロゲン原子を有していてもよいＣ２−Ｃ６アルキニル基が挙げられる。
本発明において、炭素数３〜６の脂環式炭化水素基とは、
シクロプロピル基、シクロブチル基、シクロヘキシル基等の炭素数３〜６のシクロアルキル基；
及び１−シクロヘキセニル基、３−シクロヘキセニル基等の炭素数が３〜６のシクロアルケニル基を表す。 In the present invention, the halogen atom represents a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
In the present invention, the chain hydrocarbon group having 1 to 6 carbon atoms is an alkyl group having 1 to 6 carbon atoms such as methyl group, ethyl group, propyl group, isopropyl group, hexyl group;
An alkenyl group having 1 to 6 carbon atoms such as vinyl group, 1-propenyl group, 2-propenyl group and 1-hexenyl group;
And an alkynyl group having 1 to 6 carbon atoms such as an ethynyl group, a propargyl group, a 1-pentynyl group, and a 1-hexynyl group.
In the present invention, examples of the C1-C6 chain hydrocarbon group which may have a halogen atom include a methyl group, an ethyl group, an isopropyl group, a butyl group, a tert-butyl group, a hexyl group, and a fluoromethyl group. Group, chloromethyl group, bromomethyl group, iodomethyl group, difluoromethyl group, dichloromethyl group, trifluoromethyl group, trichloromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2,2-difluoroethyl group, 2, A C1-C6 alkyl group optionally having a halogen atom, such as a 2,2-trifluoroethyl group, a pentafluoroethyl group, a heptafluoropropyl group;
Halogens such as vinyl, 2-propenyl, 1-methylvinyl, 2-methyl-1-propenyl, 3-butenyl, 1-hexenyl, 1,1-difluoroallyl, and pentafluoroallyl A C2-C6 alkenyl group optionally having atoms;
And a C2-C6 alkynyl group which may have a halogen atom such as an ethynyl group, a propargyl group, a 3-butynyl group, a 1-hexynyl group, and a 4,4,4-trifluoro-2-butynyl group. It is done.
In the present invention, an alicyclic hydrocarbon group having 3 to 6 carbon atoms is
A cycloalkyl group having 3 to 6 carbon atoms such as a cyclopropyl group, a cyclobutyl group, and a cyclohexyl group;
And a cycloalkenyl group having 3 to 6 carbon atoms such as a 1-cyclohexenyl group and a 3-cyclohexenyl group.

本発明において、スルホン酸化合物としては、例えばパラトルエンスルホン酸、ベンゼンスルホン酸、メタンスルホン酸、及びカンファースルホン酸が挙げられる。
本発明において、アミド溶媒としては、例えばＮ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミド、及びＮ−メチルピロリドンが挙げられる。
本発明において、エーテル溶媒としては、テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル、及び１，４−ジオキサンが挙げられる。 In the present invention, examples of the sulfonic acid compound include p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, and camphorsulfonic acid.
In the present invention, examples of the amide solvent include N, N-dimethylformamide, N, N-dimethylacetamide, and N-methylpyrrolidone.
In the present invention, examples of the ether solvent include tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether, and 1,4-dioxane.

（工程Ａ）
式（１）で表される化合物（以下、化合物（１）と記す。）は、式（２）で表される化合物（以下、化合物（２）と記す。）と塩化チオニルとを反応させることにより製造することができる。
該反応は、通常、溶媒中で行われる。
反応に用いられる溶媒としては、例えばトルエン、キシレン、エチルベンゼン、クロロベンゼン等の芳香族炭化水素溶媒；クロロホルム、ジクロロメタン等の含ハロゲン脂肪族炭化水素溶媒；テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル、１，４−ジオキサン等のエーテル溶媒；酢酸エチル、酢酸ブチル等のエステル溶媒；アセトニトリル、プロピオニトリル等のニトリル溶媒；ピリジン等の芳香族複素環溶媒；ジメチルスルホキシド、スルホラン等の硫黄化合物溶媒；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミド、Ｎ−メチルピロリドン等のアミド溶媒及びこれらの混合溶媒が挙げられる。好ましくは、芳香族炭化水素溶媒、含ハロゲン脂肪族炭化水素溶媒、エステル溶媒、アミド溶媒及びこれらの混合物であり、より好ましくは、芳香族炭化水素溶媒、アミド溶媒及びこれらの混合物であり、Ｎ，Ｎ−ジメチルホルムアミドが含まれることがもっとも好ましい。
溶媒の使用量は、化合物（２）１質量部に対して、通常０〜１００質量部であり、好ましくは１〜２０質量部である。
該反応には、化合物（２）１モルに対して、塩化チオニルが通常１〜１５モルの割合で用いられ、好ましくは、１〜５モル用いられる。
化合物（２）は、Ｍがカリウムであることが好ましい。
該反応の反応温度は、通常０〜１５０℃の範囲であり、好ましくは０〜８０℃である。
該反応の反応時間は通常０．１〜２４時間の範囲であり、好ましくは０．１〜１２時間である。
反応終了後は、余剰の塩化チオニルを留去などにより除去したのち、そのまま工程Ｂに用いてもよいし、蒸留精製してもよい。また、副生する塩化リチウム、塩化ナトリウム又は塩化カリウムをろ過により除去し、ろ液を濃縮することにより、化合物（１）を単離することができる。 (Process A)
A compound represented by formula (1) (hereinafter referred to as compound (1)) is obtained by reacting a compound represented by formula (2) (hereinafter referred to as compound (2)) with thionyl chloride. Can be manufactured.
The reaction is usually performed in a solvent.
Examples of the solvent used in the reaction include aromatic hydrocarbon solvents such as toluene, xylene, ethylbenzene, and chlorobenzene; halogen-containing aliphatic hydrocarbon solvents such as chloroform and dichloromethane; tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether, 1 Ether solvents such as 1,4-dioxane; ester solvents such as ethyl acetate and butyl acetate; nitrile solvents such as acetonitrile and propionitrile; aromatic heterocyclic solvents such as pyridine; sulfur compound solvents such as dimethyl sulfoxide and sulfolane; Examples thereof include amide solvents such as N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, and mixed solvents thereof. Preferably, it is an aromatic hydrocarbon solvent, a halogen-containing aliphatic hydrocarbon solvent, an ester solvent, an amide solvent and a mixture thereof, more preferably an aromatic hydrocarbon solvent, an amide solvent and a mixture thereof, N, Most preferably, N-dimethylformamide is included.
The usage-amount of a solvent is 0-100 mass parts normally with respect to 1 mass part of compounds (2), Preferably it is 1-20 mass parts.
In the reaction, thionyl chloride is usually used at a ratio of 1 to 15 mol, preferably 1 to 5 mol, per 1 mol of compound (2).
In the compound (2), M is preferably potassium.
The reaction temperature of the reaction is usually in the range of 0 to 150 ° C, preferably 0 to 80 ° C.
The reaction time is usually in the range of 0.1 to 24 hours, preferably 0.1 to 12 hours.
After completion of the reaction, excess thionyl chloride may be removed by distillation or the like, and then used directly in Step B or may be purified by distillation. Further, compound (1) can be isolated by removing by-product lithium chloride, sodium chloride or potassium chloride by filtration and concentrating the filtrate.

化合物（２）は、式

Figure 2016027019
で表される２−ピリジンカルボン酸と、アルカリ金属水酸化物（水酸化ナトリウム、水酸化カリウム、水酸化リチウム）、アルカリ金属炭酸塩（炭酸ナトリウム、炭酸カリウム、炭酸リチウム）及びアルカリ金属炭酸水素塩（炭酸水素ナトリウム、炭酸水素カリウム、炭酸水素リチウム）等の無機塩基とを、アルコール溶媒（メタノール、エタノール、２−プロパノール等）等の溶媒中で反応させることにより製造することができる。 Compound (2) has the formula
Figure 2016027019
2-pyridinecarboxylic acid, alkali metal hydroxide (sodium hydroxide, potassium hydroxide, lithium hydroxide), alkali metal carbonate (sodium carbonate, potassium carbonate, lithium carbonate) and alkali metal bicarbonate It can be produced by reacting an inorganic base such as (sodium hydrogen carbonate, potassium hydrogen carbonate, lithium hydrogen carbonate) in a solvent such as an alcohol solvent (methanol, ethanol, 2-propanol, etc.).

（工程Ｂ）
式（３）で表される化合物（以下、化合物（３）と記す。）は、化合物（１）と式（５）で表される化合物（以下、化合物（５）と記す。）とを反応させることにより製造することができる。
該反応は、通常、溶媒中で行われる。
反応に用いられる溶媒としては、例えばトルエン、キシレン、エチルベンゼン、クロロベンゼン等の芳香族炭化水素溶媒；クロロホルム、ジクロロメタン等の含ハロゲン脂肪族炭化水素溶媒；テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル、１，４−ジオキサン等のエーテル溶媒；酢酸エチル、酢酸ブチル等のエステル溶媒；アセトニトリル、プロピオニトリル等のニトリル溶媒；ピリジン等の芳香族複素環溶媒；ジメチルスルホキシド、スルホラン等の硫黄化合物溶媒；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミド、Ｎ−メチルピロリドン等のアミド溶媒及びこれらの混合溶媒が挙げられ、エーテル溶媒が含まれることが好ましく、テトラヒドロフランが含まれることがより好ましい。
溶媒の使用量は、化合物（１）１質量部に対して、通常１〜１００質量部であり、好ましくは１〜２０質量部である。
該反応は、必要に応じて塩基を加えてもよい。
反応に用いられる塩基としては、炭酸ナトリウム、炭酸カリウム等のアルカリ金属炭酸塩類；炭酸水素ナトリウム、炭酸水素カリウム等のアルカリ金属炭酸水素塩類；トリエチルアミン、Ｎ，Ｎ−ジイソプロピルエチルアミン、１，４−ジアザビシクロ［２．２．２］オクタン、１，８−ジアザビシクロ［５．４．０］ウンデセン、ピリジン、４−ジメチルアミノピリジン等の第３級アミン類等が挙げられる。
該反応には、化合物（５）１モルに対して、化合物（１）が通常１〜３モルの割合、塩基が通常１〜１０モルの割合で用いられ、好ましくは化合物（１）が通常１〜１．５モルの割合、塩基が通常１〜３モルの割合で用いられる。
該反応の反応温度は、通常−２０〜１００℃の範囲であり、好ましくは０〜８０℃である。該反応の反応時間は通常０．１〜２４時間の範囲であり、好ましくは０．１〜１２時間である。
反応終了後、化合物（３）は塩酸塩を形成しており、析出している結晶をろ過することにより化合物（３）の塩酸塩を単離し、そのまま工程Ｃに使用してもよい。また、単離することなく工程Ｃに用いる場合は、沸点が１００℃以上の溶媒に置換して、工程Ｃに用いてもよい。
また、反応混合物に水を加えた後、必要に応じて炭酸水素ナトリウム水溶液などの塩基で中和した後、有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、化合物（３）を単離することができる。単離された化合物（３）は、クロマトグラフィー、再結晶等によりさらに精製することもできる。また、化合物（３）は水和物や溶媒和物の形態で取り出すこともでき、そのまま工程Ｃに使用することができる。
さらに、化合物（３）は硫酸、塩酸、臭化水素酸、ヨウ化水素酸などの無機酸；パラトルエンスルホン酸、ベンゼンスルホン酸、メタンスルホン酸、カンファースルホン酸などのスルホン酸化合物；と混合することにより、塩の形態で取り出し、そのまま工程Ｃに使用することもできる。 (Process B)
A compound represented by formula (3) (hereinafter referred to as compound (3)) is obtained by reacting compound (1) with a compound represented by formula (5) (hereinafter referred to as compound (5)). Can be manufactured.
The reaction is usually performed in a solvent.
Examples of the solvent used in the reaction include aromatic hydrocarbon solvents such as toluene, xylene, ethylbenzene, and chlorobenzene; halogen-containing aliphatic hydrocarbon solvents such as chloroform and dichloromethane; tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether, 1 Ether solvents such as 1,4-dioxane; ester solvents such as ethyl acetate and butyl acetate; nitrile solvents such as acetonitrile and propionitrile; aromatic heterocyclic solvents such as pyridine; sulfur compound solvents such as dimethyl sulfoxide and sulfolane; Examples include amide solvents such as N-dimethylformamide, N, N-dimethylacetamide, and N-methylpyrrolidone, and mixed solvents thereof. Ether solvents are preferably included, and tetrahydrofuran is included. Ri preferred.
The usage-amount of a solvent is 1-100 mass parts normally with respect to 1 mass part of compounds (1), Preferably it is 1-20 mass parts.
In the reaction, a base may be added as necessary.
Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; triethylamine, N, N-diisopropylethylamine, 1,4-diazabicyclo [ 2.2.2] tertiary amines such as octane, 1,8-diazabicyclo [5.4.0] undecene, pyridine, 4-dimethylaminopyridine and the like.
In the reaction, with respect to 1 mol of the compound (5), the compound (1) is usually used in a proportion of 1 to 3 mol, and the base is usually used in a proportion of 1 to 10 mol, preferably the compound (1) is usually 1 A proportion of ˜1.5 mol and a base are usually used in a proportion of 1 to 3 mol.
The reaction temperature of the reaction is usually in the range of -20 to 100 ° C, preferably 0 to 80 ° C. The reaction time is usually in the range of 0.1 to 24 hours, preferably 0.1 to 12 hours.
After completion of the reaction, the compound (3) forms a hydrochloride, and the hydrochloride of the compound (3) may be isolated by filtering the precipitated crystals and used in Step C as it is. Moreover, when using for the process C without isolating, you may substitute for the solvent whose boiling point is 100 degreeC or more, and you may use for the process C.
In addition, by adding water to the reaction mixture, neutralizing with a base such as an aqueous sodium hydrogen carbonate solution as necessary, and then performing post-treatment operations such as extraction with an organic solvent and drying and concentration of the organic layer. Compound (3) can be isolated. The isolated compound (3) can be further purified by chromatography, recrystallization and the like. Compound (3) can also be taken out in the form of a hydrate or a solvate, and can be used in Step C as it is.
Further, the compound (3) is mixed with an inorganic acid such as sulfuric acid, hydrochloric acid, hydrobromic acid or hydroiodic acid; a sulfonic acid compound such as paratoluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid or camphorsulfonic acid; Thus, it can be taken out in the form of a salt and used in the step C as it is.

（工程Ｃ）
式（４）で表される化合物（以下、化合物（４）と記す。）は、化合物（３）またはその酸塩を、酸の存在下で１００℃〜１８０℃で環化することにより製造することができる。
環化に用いられる酸としては、硫酸、塩酸、臭化水素酸、ヨウ化水素酸などの無機酸；パラトルエンスルホン酸、ベンゼンスルホン酸、メタンスルホン酸、カンファースルホン酸などのスルホン酸化合物；又は、アンバーライト（登録商標）酸性イオン交換樹脂；が挙げられ、好ましくはスルホン酸化合物が挙げられ、より好ましくは、パラトルエンスルホン酸、メタンスルホン酸が挙げられる。
該環化は、通常、溶媒中で行われる。
環化に用いられる溶媒としては、例えばトルエン、キシレン、エチルベンゼン、クロロベンゼン、クメン、メシチレン、ジクロロベンゼン等の芳香族炭化水素溶媒；１，４−ジオキサン等のエーテル溶媒；酢酸ブチル等のエステル溶媒；プロピオニトリル等のニトリル溶媒；ピリジン等の芳香族複素環溶媒；ジメチルスルホキシド、スルホラン等の硫黄化合物溶媒；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミド、Ｎ−メチルピロリドン等のアミド溶媒及びこれらの混合溶媒が挙げられ、好ましくは、芳香族炭化水素溶媒が挙げられ、より好ましくは、キシレン、クロロベンゼンが挙げられる。
溶媒の使用量は、化合物（３）１質量部に対して、通常１〜１００質量部であり、好ましくは１〜２０質量部である。
該環化には、化合物（３）１モルに対して、酸が通常０．１モル〜５モルの割合で用いられ、好ましくは酸が０．５モル〜３モルの割合で用いられる。
該環化の温度は、通常、１００〜１８０℃の範囲であり、好ましくは１００〜１６０℃である。該環化の時間は、通常、０．１〜４８時間の範囲であり、好ましくは０．１〜２４時間である。
該環化は原料に含まれる水や環化で生じる水を除去することが好ましい。除去する方法としては、ディーンスターク装置等を用いて共沸脱水により除去する方法や、モレキュラーシーブス、無水硫酸ナトリウムおよび、無水硫酸マグネシウムなどの脱水剤を用いて除去する方法があげられ、共沸脱水により除去する方法が好ましい。
該環化は、分解生成物などの除去を目的とし、活性炭、シリカゲル、セライト（登録商標）などの吸着剤；を添加してもよい。
環化終了後は、得られた混合物を水又は炭酸水素ナトリウム水溶液などの塩基性の水溶液に加えてから有機溶媒抽出し、有機層を濃縮する；得られた混合物を水に加えて生じた固体を濾過により集める；又は、得られた混合物中に生成した固体を濾過により集めることにより化合物（４）を単離することができる。単離された化合物（４）は、再結晶、クロマトグラフィ−等により更に精製することもできる。また、化合物（４）は塩酸、臭化水素酸、ヨウ化水素酸などの無機酸；パラトルエンスルホン酸、ベンゼンスルホン酸、メタンスルホン酸、カンファースルホン酸などのスルホン酸化合物；と混合することにより、塩の形態で取り出すこともできる。 (Process C)
A compound represented by formula (4) (hereinafter referred to as compound (4)) is produced by cyclizing compound (3) or an acid salt thereof at 100 ° C. to 180 ° C. in the presence of an acid. be able to.
Examples of the acid used for cyclization include inorganic acids such as sulfuric acid, hydrochloric acid, hydrobromic acid and hydroiodic acid; sulfonic acid compounds such as paratoluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid and camphorsulfonic acid; or And Amberlite (registered trademark) acidic ion exchange resin, preferably sulfonic acid compounds, more preferably paratoluenesulfonic acid and methanesulfonic acid.
The cyclization is usually performed in a solvent.
Examples of the solvent used for the cyclization include aromatic hydrocarbon solvents such as toluene, xylene, ethylbenzene, chlorobenzene, cumene, mesitylene and dichlorobenzene; ether solvents such as 1,4-dioxane; ester solvents such as butyl acetate; Nitrile solvents such as pionitrile; aromatic heterocyclic solvents such as pyridine; sulfur compound solvents such as dimethyl sulfoxide and sulfolane; amide solvents such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methylpyrrolidone and these And preferably include aromatic hydrocarbon solvents, and more preferably xylene and chlorobenzene.
The usage-amount of a solvent is 1-100 mass parts normally with respect to 1 mass part of compounds (3), Preferably it is 1-20 mass parts.
For the cyclization, an acid is usually used in a proportion of 0.1 mol to 5 mol, preferably an acid is used in a proportion of 0.5 mol to 3 mol, relative to 1 mol of the compound (3).
The cyclization temperature is usually in the range of 100 to 180 ° C, preferably 100 to 160 ° C. The cyclization time is usually in the range of 0.1 to 48 hours, preferably 0.1 to 24 hours.
The cyclization preferably removes water contained in the raw material or water generated by cyclization. Examples of the removal method include a method of removing by azeotropic dehydration using a Dean Stark apparatus or the like, and a method of removing using a dehydrating agent such as molecular sieves, anhydrous sodium sulfate, and anhydrous magnesium sulfate. The method of removing by is preferable.
The cyclization is intended to remove decomposition products and the like, and an adsorbent such as activated carbon, silica gel or Celite (registered trademark) may be added.
After completion of the cyclization, the resulting mixture is added to water or a basic aqueous solution such as aqueous sodium hydrogen carbonate solution, extracted with an organic solvent, and the organic layer is concentrated; the resulting mixture is added to water to form a solid Can be collected by filtration; or compound (4) can be isolated by collecting the solid formed in the resulting mixture by filtration. The isolated compound (4) can be further purified by recrystallization, chromatography or the like. Compound (4) is mixed with an inorganic acid such as hydrochloric acid, hydrobromic acid or hydroiodic acid; a sulfonic acid compound such as paratoluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid or camphorsulfonic acid; It can also be taken out in the form of a salt.

以下、本発明を実施例によりさらに説明するが、本発明はこれらの例に限定されない。   EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not limited to these examples.

実施例１

Figure 2016027019
窒素雰囲気下で、（３−エチルスルホニル）−２−ピリジンカルボン酸カリウム０．５０ｇ、キシレン２．５０ｇ及びＮ，Ｎ−ジメチルホルムアミド０．０１ｇを混合し、６０℃に加熱したのち塩化チオニル０．３５ｇを５時間かけて滴下し、６０℃で４時間攪拌した。反応液にイソブチルアミンを加え、高速液体クロマトグラフィーを用いた内部標準法（内部標準物質；ビフェニル）で定量したところ、（３−エチルスルホニル）−２−ピリジンカルボン酸クロリドを収率９５．１％で得た。 Example 1
Figure 2016027019
Under a nitrogen atmosphere, 0.50 g of potassium (3-ethylsulfonyl) -2-pyridinecarboxylate, 2.50 g of xylene and 0.01 g of N, N-dimethylformamide were mixed and heated to 60 ° C. 35g was dripped over 5 hours, and it stirred at 60 degreeC for 4 hours. When isobutylamine was added to the reaction solution and quantified by an internal standard method (internal standard substance; biphenyl) using high performance liquid chromatography, (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride was obtained in a yield of 95.1%. Got in.

実施例２

Figure 2016027019
窒素雰囲気下で、キシレン２５．００ｇ、Ｎ，Ｎ−ジメチルホルムアミド０．０７ｇ及び塩化チオニル４．８０ｇを混合し、６０℃に加熱したのち、（３−エチルスルホニル）−２−ピリジンカルボン酸カリウム５．００ｇを５時間かけて添加し、６０℃で４時間攪拌した。反応液にイソブチルアミンを加え、高速液体クロマトグラフィーを用いた内部標準法（内部標準物質；ビフェニル）で定量したところ、（３−エチルスルホニル）−２−ピリジンカルボン酸クロリドを収率９６．９％で得た。 Example 2
Figure 2016027019
In a nitrogen atmosphere, 25.00 g of xylene, 0.07 g of N, N-dimethylformamide and 4.80 g of thionyl chloride were mixed and heated to 60 ° C., and then potassium (3-ethylsulfonyl) -2-pyridinecarboxylate 5 0.000 g was added over 5 hours and stirred at 60 ° C. for 4 hours. When isobutylamine was added to the reaction solution and quantified by an internal standard method (internal standard substance; biphenyl) using high performance liquid chromatography, (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride was obtained in a yield of 96.9%. Got in.

実施例３

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルフィニル）フェノール１．８０ｇ及びテトラヒドロフラン９．００ｇを混合し、０℃に冷却したのち（３−エチルスルホニル）−２−ピリジンカルボン酸クロリド１．９５ｇとキシレン３．９０ｇの混合物を１時間かけて滴下し、０℃で４時間攪拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出し、有機層を減圧下濃縮することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミドを収率９５．６％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１１．４７（１Ｈ，ｂｒｓ），１０．４２（１Ｈ，ｓ），８．９７（１Ｈ，ｄｄ），８．７４（１Ｈ，ｓ），８．４３（１Ｈ，ｄ），７．８８（１Ｈ，ｄｄ），７．５８（１Ｈ，ｄｄ），７．２５（１Ｈ，ｄ），３．６８（２Ｈ，ｑ），１．１８（３Ｈ，ｔ）．
なお、２−アミノ−４−（トリフルオロメチルスルフィニル）フェノールは以下の方法により合成した。
２−ニトロ−４−（トリフルオロメチルスルフィニル）フェノール５．０ｇ、パラジウムカーボン（Ｐｄ５％）０．５０ｇ及びエタノール６５ｍｌの混合物を、水素雰囲気下３５℃で６時間攪拌した。室温まで放冷した反応混合物をセライト（登録商標）でろ過し、水を加え、酢酸エチルで抽出した。有機層を水で洗浄した後、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた固体をクロロホルムで洗浄することにより、２−アミノ−４−（トリフルオロメチルスルフィニル）フェノール３．８７ｇを得た。 Example 3
Figure 2016027019
Under a nitrogen atmosphere, 1.80 g of 2-amino-4- (trifluoromethylsulfinyl) phenol and 9.00 g of tetrahydrofuran were mixed, cooled to 0 ° C., and (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride 1 A mixture of .95 g and 3.90 g of xylene was added dropwise over 1 hour, and the mixture was stirred at 0 ° C. for 4 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated under reduced pressure to give 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl] picoline. The amide was obtained in 95.6% yield.
1 H-NMR (DMSO-d 6 ) δ: 11.47 (1H, brs), 10.42 (1H, s), 8.97 (1H, dd), 8.74 (1H, s), 8. 43 (1H, d), 7.88 (1H, dd), 7.58 (1H, dd), 7.25 (1H, d), 3.68 (2H, q), 1.18 (3H, t ).
In addition, 2-amino-4- (trifluoromethylsulfinyl) phenol was synthesized by the following method.
A mixture of 5.0 g of 2-nitro-4- (trifluoromethylsulfinyl) phenol, 0.50 g of palladium carbon (Pd 5%) and 65 ml of ethanol was stirred at 35 ° C. for 6 hours under a hydrogen atmosphere. The reaction mixture was allowed to cool to room temperature, filtered through Celite (registered trademark), water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained solid was washed with chloroform to obtain 3.87 g of 2-amino-4- (trifluoromethylsulfinyl) phenol.

実施例４

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルフィニル）フェノール１２．００ｇ及びテトラヒドロフラン２４．００ｇを混合し、６０℃に昇温したのち（３−エチルスルホニル）−２−ピリジンカルボン酸クロリド１１．９９ｇとキシレン２４．００ｇとの混合物を１時間かけて滴下し、６０℃で４時間攪拌した。反応混合物に８％水酸化ナトリウム水溶液を加え、０℃に冷却したのち、析出した固形物をろ過することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミド・テトラヒドロフラン和物を収率９２．８％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１１．４７（１Ｈ，ｂｒｓ），１０．４２（１Ｈ，ｓ），８．９７（１Ｈ，ｄｄ），８．７４（１Ｈ，ｓ），８．４３（１Ｈ，ｄ），７．８８（１Ｈ，ｄｄ），７．５８（１Ｈ，ｄｄ），７．２５（１Ｈ，ｄ），３．６８（６Ｈ，ｍ），１．８０（４Ｈ，ｍ），１．１８（３Ｈ，ｔ）． Example 4
Figure 2016027019
Under a nitrogen atmosphere, 12.00 g of 2-amino-4- (trifluoromethylsulfinyl) phenol and 24.00 g of tetrahydrofuran were mixed, and the temperature was raised to 60 ° C., then (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride A mixture of 11.99 g and xylene 24.00 g was added dropwise over 1 hour and stirred at 60 ° C. for 4 hours. An 8% aqueous sodium hydroxide solution was added to the reaction mixture, and after cooling to 0 ° C., the precipitated solid was filtered to give 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl. A picolinamide / tetrahydrofuran hydrate was obtained in a yield of 92.8%.
1 H-NMR (DMSO-d 6 ) δ: 11.47 (1H, brs), 10.42 (1H, s), 8.97 (1H, dd), 8.74 (1H, s), 8. 43 (1H, d), 7.88 (1H, dd), 7.58 (1H, dd), 7.25 (1H, d), 3.68 (6H, m), 1.80 (4H, m ), 1.18 (3H, t).

実施例５

Figure 2016027019
窒素雰囲気下で、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミド・テトラヒドロフラン和物１０．００ｇ及び水５０．００ｇを混合し、８０℃に昇温したのち、４時間攪拌した。反応混合物を０℃に冷却したのち、析出した固形物をろ過することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミド・１水和物を収率９２．８％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１１．４７（１Ｈ，ｂｒｓ），１０．４２（１Ｈ，ｓ），８．９７（１Ｈ，ｄｄ），８．７４（１Ｈ，ｓ），８．４３（１Ｈ，ｄ），７．８８（１Ｈ，ｄｄ），７．５８（１Ｈ，ｄｄ），７．２５（１Ｈ，ｄ），３．６８（２Ｈ，ｍ），３．３４（２Ｈ，ｍ），１．１８（３Ｈ，ｔ）． Example 5
Figure 2016027019
Under a nitrogen atmosphere, 10.00 g of 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl] picolinamide / tetrahydrofuran hydrate and 50.00 g of water were mixed, and the temperature was raised to 80 ° C. After that, the mixture was stirred for 4 hours. After cooling the reaction mixture to 0 ° C., the precipitated solid was filtered to give 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl] picolinamide monohydrate. The yield was 92.8%.
1 H-NMR (DMSO-d 6 ) δ: 11.47 (1H, brs), 10.42 (1H, s), 8.97 (1H, dd), 8.74 (1H, s), 8. 43 (1H, d), 7.88 (1H, dd), 7.58 (1H, dd), 7.25 (1H, d), 3.68 (2H, m), 3.34 (2H, m ), 1.18 (3H, t).

実施例６

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルフィニル）フェノール５．００ｇ及びＮ，Ｎ−ジメチルアセトアミド１０．００ｇを混合し、６０℃に昇温したのち（３−エチルスルホニル）−２−ピリジンカルボン酸クロリド５．００ｇとキシレン１０．００ｇとの混合物を１時間かけて滴下し、６０℃で４時間攪拌した。反応混合物に８％水酸化ナトリウム水溶液を加え、０℃に冷却したのち、析出した固形物をろ過することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミド・Ｎ，Ｎ−ジメチルアセトアミド和物を収率８９．１％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１１．４７（１Ｈ，ｂｒｓ），１０．４２（１Ｈ，ｓ），８．９７（１Ｈ，ｄｄ），８．７４（１Ｈ，ｓ），８．４３（１Ｈ，ｄ），７．８８（１Ｈ，ｄｄ），７．５８（１Ｈ，ｄｄ），７．２５（１Ｈ，ｄ），３．６８（２Ｈ，ｑ），２．９５（３Ｈ，ｍ），２．７９（３Ｈ，ｍ），１．９６（３Ｈ，ｍ），１．１８（３Ｈ，ｔ）． Example 6
Figure 2016027019
Under a nitrogen atmosphere, 5.00 g of 2-amino-4- (trifluoromethylsulfinyl) phenol and 10.00 g of N, N-dimethylacetamide were mixed and heated to 60 ° C. (3-ethylsulfonyl) -2 A mixture of 5.00 g of pyridinecarboxylic acid chloride and 10.00 g of xylene was added dropwise over 1 hour, and the mixture was stirred at 60 ° C. for 4 hours. An 8% aqueous sodium hydroxide solution was added to the reaction mixture, and after cooling to 0 ° C., the precipitated solid was filtered to give 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl. A picolinamide.N, N-dimethylacetamide solvate was obtained in a yield of 89.1%.
1 H-NMR (DMSO-d 6 ) δ: 11.47 (1H, brs), 10.42 (1H, s), 8.97 (1H, dd), 8.74 (1H, s), 8. 43 (1H, d), 7.88 (1H, dd), 7.58 (1H, dd), 7.25 (1H, d), 3.68 (2H, q), 2.95 (3H, m ), 2.79 (3H, m), 1.96 (3H, m), 1.18 (3H, t).

実施例７

Figure 2016027019
窒素雰囲気下で、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミド１．００ｇ、ｐ−トルエンスルホン酸一水和物０．６６ｇ及びキシレン５．００ｇの混合物を、１５５℃で２０時間還流脱水した。室温まで放冷した混合物を飽和炭酸水素ナトリウム水溶液に加え、分液したのちに、有機層にｎ−ヘプタン５．００ｇを加え、冷却晶析を行い、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルフィニル）ベンズオキサゾールを収率８８．２％で得た。
1Ｈ−ＮＭＲ（ＣＤＣｌ3）δ：９．０４（１Ｈ，ｄｄ），８．６１（１Ｈ，ｄｄ），８．３５（１Ｈ，ｄ），７．９６−７．８６（２Ｈ，ｍ），７．７７（１Ｈ，ｄｄ），４．０１（２Ｈ，ｑ），１．４４（３Ｈ，ｔ）． Example 7
Figure 2016027019
Under a nitrogen atmosphere, 1.00 g of 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl] picolinamide, 0.66 g of p-toluenesulfonic acid monohydrate and 5.00 g of xylene The mixture was reflux-dehydrated at 155 ° C. for 20 hours. The mixture allowed to cool to room temperature was added to a saturated aqueous sodium hydrogen carbonate solution, and after liquid separation, 5.00 g of n-heptane was added to the organic layer, cooling crystallization was performed, and 2- (3-ethylsulfonylpyridine-2- Yl) -5- (trifluoromethylsulfinyl) benzoxazole was obtained in a yield of 88.2%.
1 H-NMR (CDCl 3 ) δ: 9.04 (1H, dd), 8.61 (1H, dd), 8.35 (1H, d), 7.96-7.86 (2H, m), 7.77 (1H, dd), 4.01 (2H, q), 1.44 (3H, t).

実施例８

Figure 2016027019
窒素雰囲気下で、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミド０．３０ｇ、ｐ−トルエンスルホン酸一水和物０．２０ｇ及びメシチレン１．５０ｇの混合物を、１８０℃で７時間還流脱水した。室温まで放冷した混合物を飽和炭酸水素ナトリウム水溶液に加え、分液したのち、得られた有機層を高速液体クロマトグラフィーを用いた内部標準法（内部標準物質；ビフェニル）で分析したところ、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルフィニル）ベンズオキサゾールを収率８１．８％で得た。 Example 8
Figure 2016027019
Under a nitrogen atmosphere, 0.30 g of 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl] picolinamide, 0.20 g of p-toluenesulfonic acid monohydrate and 1.50 g of mesitylene The mixture was reflux-dehydrated at 180 ° C. for 7 hours. The mixture was allowed to cool to room temperature and added to a saturated aqueous solution of sodium hydrogen carbonate. After separation, the resulting organic layer was analyzed by an internal standard method (internal standard substance; biphenyl) using high performance liquid chromatography. (3-Ethylsulfonylpyridin-2-yl) -5- (trifluoromethylsulfinyl) benzoxazole was obtained in a yield of 81.8%.

実施例９

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルホニル）フェノール１．８０ｇ及びテトラヒドロフラン９．００ｇを混合し、０℃に冷却したのちに（３−エチルスルホニル）−２−ピリジンカルボン酸クロリド１．９１ｇとキシレン３．８２ｇとの混合物を１時間かけて滴下し、０℃で４時間攪拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出し、有機層を減圧下濃縮することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルホニル）フェニル］ピコリンアミドを収率９６．７％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１２．６６（１Ｈ，ｂｒｓ），１０．４２（１Ｈ，ｓ），８．９７（１Ｈ，ｄｄ），８．８５（１Ｈ，ｄ），８．４３（１Ｈ，ｄｄ），７．８８（１Ｈ，ｄｄ），７．８２（１Ｈ，ｄｄ），７．３２（１Ｈ，ｄ），３．６８（２Ｈ，ｑ），１．１９（３Ｈ，ｔ）． Example 9
Figure 2016027019
Under a nitrogen atmosphere, 1.80 g of 2-amino-4- (trifluoromethylsulfonyl) phenol and 9.00 g of tetrahydrofuran were mixed, cooled to 0 ° C., and (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride. A mixture of 1.91 g and 3.82 g of xylene was added dropwise over 1 hour, and the mixture was stirred at 0 ° C. for 4 hours. Saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated under reduced pressure to give 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfonyl) phenyl] picoline. The amide was obtained in 96.7% yield.
1 H-NMR (DMSO-d 6 ) δ: 12.66 (1H, brs), 10.42 (1H, s), 8.97 (1H, dd), 8.85 (1H, d), 8. 43 (1H, dd), 7.88 (1H, dd), 7.82 (1H, dd), 7.32 (1H, d), 3.68 (2H, q), 1.19 (3H, t ).

実施例１０

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルホニル）フェノール１０．００ｇ及びテトラヒドロフラン５０．００ｇを混合し、０℃に冷却したのちに（３−エチルスルホニル）−２−ピリジンカルボン酸クロリド１２．３５ｇとテトラヒドロフラン２７．００ｇとの混合物を１時間かけて滴下し、０℃で４時間攪拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、減圧下濃縮し、残渣を酢酸エチルで抽出し、有機層を減圧下濃縮することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルホニル）フェニル］ピコリンアミドを収率９３．４％で得た。 Example 10
Figure 2016027019
Under a nitrogen atmosphere, 10.00 g of 2-amino-4- (trifluoromethylsulfonyl) phenol and 50.00 g of tetrahydrofuran were mixed, cooled to 0 ° C., and then (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride. A mixture of 12.35 g and 27.00 g of tetrahydrofuran was added dropwise over 1 hour, and the mixture was stirred at 0 ° C. for 4 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, the mixture was concentrated under reduced pressure, the residue was extracted with ethyl acetate, and the organic layer was concentrated under reduced pressure to give 3-ethylsulfonyl-N- [2-hydroxy-5- (tri Fluoromethylsulfonyl) phenyl] picolinamide was obtained in 93.4% yield.

実施例１１

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルホニル）フェノール１２．００ｇ及びテトラヒドロフラン２４．００ｇを混合し、６０℃に昇温したのち（３−エチルスルホニル）−２−ピリジンカルボン酸クロリド１１．９９ｇとキシレン２４．００ｇとの混合物を１時間かけて滴下し、６０℃で４時間攪拌した。反応混合物に８％水酸化ナトリウム水溶液を加え、０℃に冷却したのち、析出した固形物をろ過することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルホニル）フェニル］ピコリンアミド・テトラヒドロフラン和物を収率９１．５％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１２．６６（１Ｈ，ｂｒｓ），１０．４２（１Ｈ，ｓ），８．９７（１Ｈ，ｄｄ），８．８５（１Ｈ，ｄ），８．４３（１Ｈ，ｄｄ），７．８８（１Ｈ，ｄｄ），７．８２（１Ｈ，ｄｄ），７．３２（１Ｈ，ｄ），３．６８（６Ｈ，ｍ），１．８０（４Ｈ，ｍ），１．１８（３Ｈ，ｔ）． Example 11
Figure 2016027019
Under a nitrogen atmosphere, 2-amino-4- (trifluoromethylsulfonyl) phenol (12.00 g) and tetrahydrofuran (24.00 g) were mixed, and the temperature was raised to 60 ° C. and then (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride. A mixture of 11.99 g and xylene 24.00 g was added dropwise over 1 hour and stirred at 60 ° C. for 4 hours. After adding 8% aqueous sodium hydroxide solution to the reaction mixture and cooling to 0 ° C., the precipitated solid was filtered to give 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfonyl) phenyl. A picolinamide / tetrahydrofuran hydrate was obtained in a yield of 91.5%.
1 H-NMR (DMSO-d 6 ) δ: 12.66 (1H, brs), 10.42 (1H, s), 8.97 (1H, dd), 8.85 (1H, d), 8. 43 (1H, dd), 7.88 (1H, dd), 7.82 (1H, dd), 7.32 (1H, d), 3.68 (6H, m), 1.80 (4H, m ), 1.18 (3H, t).

実施例１２

Figure 2016027019
窒素雰囲気下で、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルホニル）フェニル］ピコリンアミド・テトラヒドロフラン和物１０．００ｇ及び水５０．００ｇを混合し、８０℃に昇温したのち、４時間攪拌した。反応混合物を０℃に冷却したのち、析出した固形物をろ過することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルホニル）フェニル］ピコリンアミド・１水和物を収率９７．９％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１２．６６（１Ｈ，ｂｒｓ），１０．４２（１Ｈ，ｓ），８．９７（１Ｈ，ｄｄ），８．８５（１Ｈ，ｄ），８．４３（１Ｈ，ｄｄ），７．８８（１Ｈ，ｄｄ），７．８２（１Ｈ，ｄｄ），７．３２（１Ｈ，ｄ），３．６８（２Ｈ，ｍ），３．３４（２Ｈ，ｍ），１．１８（３Ｈ，ｔ）． Example 12
Figure 2016027019
Under a nitrogen atmosphere, 10.00 g of 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfonyl) phenyl] picolinamide / tetrahydrofuran hydrate and 50.00 g of water were mixed, and the temperature was raised to 80 ° C. After that, the mixture was stirred for 4 hours. After cooling the reaction mixture to 0 ° C., the precipitated solid was filtered to give 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfonyl) phenyl] picolinamide monohydrate. The yield was 97.9%.
1 H-NMR (DMSO-d 6 ) δ: 12.66 (1H, brs), 10.42 (1H, s), 8.97 (1H, dd), 8.85 (1H, d), 8. 43 (1H, dd), 7.88 (1H, dd), 7.82 (1H, dd), 7.32 (1H, d), 3.68 (2H, m), 3.34 (2H, m ), 1.18 (3H, t).

実施例１３

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルホニル）フェノール５．００ｇ及びＮ，Ｎ−ジメチルアセトアミド１０．００ｇを混合し、６０℃に昇温したのち（３−エチルスルホニル）−２−ピリジンカルボン酸クロリド５．００ｇとキシレン１０．００ｇとの混合物を１時間かけて滴下し、６０℃で４時間攪拌した。反応混合物に８％水酸化ナトリウム水溶液を加え、０℃に冷却したのち、析出した固形物をろ過することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルホニル）フェニル］ピコリンアミド・Ｎ，Ｎ−ジメチルアセトアミド和物を収率８７．２％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１２．６６（１Ｈ，ｂｒｓ），１０．４２（１Ｈ，ｓ），８．９７（１Ｈ，ｄｄ），８．８５（１Ｈ，ｄ），８．４３（１Ｈ，ｄｄ），７．８８（１Ｈ，ｄｄ），７．８２（１Ｈ，ｄｄ），７．３２（１Ｈ，ｄ），３．６８（２Ｈ，ｑ），２．９５（３Ｈ，ｍ），２．７９（３Ｈ，ｍ），１．９６（３Ｈ，ｍ），１．１８（３Ｈ，ｔ）． Example 13
Figure 2016027019
Under a nitrogen atmosphere, 5.00 g of 2-amino-4- (trifluoromethylsulfonyl) phenol and 10.00 g of N, N-dimethylacetamide were mixed and heated to 60 ° C. (3-ethylsulfonyl) -2 A mixture of 5.00 g of pyridinecarboxylic acid chloride and 10.00 g of xylene was added dropwise over 1 hour, and the mixture was stirred at 60 ° C. for 4 hours. After adding 8% aqueous sodium hydroxide solution to the reaction mixture and cooling to 0 ° C., the precipitated solid was filtered to give 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfonyl) phenyl. A picolinamide / N, N-dimethylacetamide solvate was obtained in a yield of 87.2%.
1 H-NMR (DMSO-d 6 ) δ: 12.66 (1H, brs), 10.42 (1H, s), 8.97 (1H, dd), 8.85 (1H, d), 8. 43 (1H, dd), 7.88 (1H, dd), 7.82 (1H, dd), 7.32 (1H, d), 3.68 (2H, q), 2.95 (3H, m ), 2.79 (3H, m), 1.96 (3H, m), 1.18 (3H, t).

実施例１４

Figure 2016027019
窒素雰囲気下で、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルホニル）フェニル］ピコリンアミド１．００ｇ、ｐ−トルエンスルホン酸一水和物０．６２ｇ及びキシレン５．００ｇの混合物を、１５５℃で１５時間還流脱水した。室温まで放冷した混合物を飽和炭酸水素ナトリウム水溶液に加え、分液したのち、有機層にｎ−ヘプタン５．００ｇを加え、冷却晶析を行い、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルホニル）ベンズオキサゾールを収率８６．５％で得た。
1Ｈ−ＮＭＲ（ＣＤＣｌ3）δ：９．０５（１Ｈ，ｄｄ），８．６１（１Ｈ，ｄｄ），８．５９（１Ｈ，ｄ），８．１７（１Ｈ，ｄｄ），７．９６（１Ｈ，ｄ），７．８０（１Ｈ，ｄｄ），３．９８（２Ｈ，ｑ），１．４５（３Ｈ，ｔ）． Example 14
Figure 2016027019
Under a nitrogen atmosphere, 1.00 g of 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfonyl) phenyl] picolinamide, 0.62 g of p-toluenesulfonic acid monohydrate and 5.00 g of xylene. The mixture was reflux-dehydrated at 155 ° C. for 15 hours. The mixture was allowed to cool to room temperature and added to a saturated aqueous solution of sodium hydrogen carbonate. After liquid separation, 5.00 g of n-heptane was added to the organic layer, cooling crystallization was performed, and 2- (3-ethylsulfonylpyridin-2-yl ) -5- (trifluoromethylsulfonyl) benzoxazole was obtained in a yield of 86.5%.
1 H-NMR (CDCl 3 ) δ: 9.05 (1H, dd), 8.61 (1H, dd), 8.59 (1H, d), 8.17 (1H, dd), 7.96 ( 1H, d), 7.80 (1H, dd), 3.98 (2H, q), 1.45 (3H, t).

実施例１５

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルフィニル）フェノール２．７０ｇ及びテトラヒドロフラン８．１０ｇを混合し、０℃に冷却したのち、（３−エチルスルホニル）−２−ピリジンカルボン酸クロリド３．６４ｇとテトラヒドロフラン３．６４ｇとの混合物を４時間かけて滴下し、０℃で１２時間攪拌した。反応混合物を減圧下濃縮することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミド塩酸塩６．２１ｇを収率９６．７％で得た。
Figure 2016027019
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１２．５６（１Ｈ，ｂｒｓ），１０．４０（１Ｈ，ｓ），８．９７（１Ｈ，ｄｄ），８．８６（１Ｈ，ｄ），８．４４（１Ｈ，ｄｄ），７．８８（１Ｈ，ｄｄ），７．８１（１Ｈ，ｄｄ），７．４２（１Ｈ，ｄ），３．６８（２Ｈ，ｑ），１．２０（３Ｈ，ｔ）． Example 15
Figure 2016027019
Under a nitrogen atmosphere, 2.70 g of 2-amino-4- (trifluoromethylsulfinyl) phenol and 8.10 g of tetrahydrofuran were mixed, cooled to 0 ° C., and (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride. A mixture of 3.64 g and 3.64 g of tetrahydrofuran was added dropwise over 4 hours, and the mixture was stirred at 0 ° C. for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain 6.21 g of 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl] picolinamide hydrochloride in a yield of 96.7%.
Figure 2016027019
1 H-NMR (DMSO-d 6 ) δ: 12.56 (1H, brs), 10.40 (1H, s), 8.97 (1H, dd), 8.86 (1H, d), 8. 44 (1H, dd), 7.88 (1H, dd), 7.81 (1H, dd), 7.42 (1H, d), 3.68 (2H, q), 1.20 (3H, t ).

実施例１６

Figure 2016027019
窒素雰囲気下で、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミド塩酸塩３．００ｇ、ｐ−トルエンスルホン酸一水和物１．２４ｇ及びキシレン１５．００ｇの混合物を、１５５℃で２０時間還流脱水した。室温まで放冷した混合物を飽和炭酸水素ナトリウム水溶液に加え、分液したのち、得られた有機層を高速液体クロマトグラフィーを用いた内部標準法（内部標準物質；ビフェニル）で定量したところ、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルフィニル）ベンズオキサゾールを収率８５．０％で得た。 Example 16
Figure 2016027019
Under a nitrogen atmosphere, 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl] picolinamide hydrochloride 3.00 g, p-toluenesulfonic acid monohydrate 1.24 g and xylene 15 0.000 g of the mixture was reflux dehydrated at 155 ° C. for 20 hours. The mixture allowed to cool to room temperature was added to a saturated aqueous solution of sodium hydrogen carbonate, and after separation, the obtained organic layer was quantified by an internal standard method (internal standard substance; biphenyl) using high performance liquid chromatography. (3-Ethylsulfonylpyridin-2-yl) -5- (trifluoromethylsulfinyl) benzoxazole was obtained in a yield of 85.0%.

実施例１７

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルフィニル）フェノール３．００ｇ及びテトラヒドロフラン１２．００ｇを混合し、０℃に冷却したのちに（３−エチルスルホニル）−２−ピリジンカルボン酸クロリド４．１１ｇとキシレン７．００ｇとの混合物を４時間かけて滴下し、０℃で１２時間攪拌した。反応混合物を減圧下濃縮し、得られた残渣に、ｐ−トルエンスルホン酸一水和物５．０６ｇ及びキシレン１６．９０ｇの混合物を加え、１５５℃で２４時間還流脱水した。室温まで放冷した混合物を飽和炭酸水素ナトリウム水溶液に加え、分液したのち、得られた有機層を高速液体クロマトグラフィーを用いた内部標準法（内部標準物質；ビフェニル）で定量したところ、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルフィニル）ベンズオキサゾールを収率７９．４％で得た。 Example 17
Figure 2016027019
Under a nitrogen atmosphere, 3.00 g of 2-amino-4- (trifluoromethylsulfinyl) phenol and 12.00 g of tetrahydrofuran were mixed, cooled to 0 ° C., and (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride. A mixture of 4.11 g and 7.00 g of xylene was added dropwise over 4 hours, and the mixture was stirred at 0 ° C. for 12 hours. The reaction mixture was concentrated under reduced pressure, and a mixture of 5.06 g of p-toluenesulfonic acid monohydrate and 16.90 g of xylene was added to the resulting residue, followed by reflux dehydration at 155 ° C. for 24 hours. The mixture allowed to cool to room temperature was added to a saturated aqueous solution of sodium hydrogen carbonate, and after separation, the obtained organic layer was quantified by an internal standard method (internal standard substance; biphenyl) using high performance liquid chromatography. (3-Ethylsulfonylpyridin-2-yl) -5- (trifluoromethylsulfinyl) benzoxazole was obtained in a yield of 79.4%.

実施例１８

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルフィニル）フェノール４．３３ｇ及びテトラヒドロフラン３４．７２ｇを混合し、０℃に冷却したのち、（３−エチルスルホニル）−６−クロロ−２−ピリジンカルボン酸クロリド５．３０ｇとテトラヒドロフラン１０．６０ｇとの混合物を１時間かけて滴下し、０℃で４時間攪拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出し、有機層を減圧下濃縮することにより、３−エチルスルホニル−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミドを収率９９．２％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１１．５５（１Ｈ，ｂｒｓ），１０．４５（１Ｈ，ｓ），８．６５（１Ｈ，ｓ），８．３８（１Ｈ，ｄ），７．９６（１Ｈ，ｄ），７．５７（１Ｈ，ｄ），７．２６（１Ｈ，ｄ），３．８４（２Ｈ，ｑ），１．３２（３Ｈ，ｔ）． Example 18
Figure 2016027019
Under a nitrogen atmosphere, 4.33 g of 2-amino-4- (trifluoromethylsulfinyl) phenol and 34.72 g of tetrahydrofuran were mixed, cooled to 0 ° C., and then (3-ethylsulfonyl) -6-chloro-2- A mixture of 5.30 g of pyridinecarboxylic acid chloride and 10.60 g of tetrahydrofuran was added dropwise over 1 hour, and the mixture was stirred at 0 ° C. for 4 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated under reduced pressure to give 3-ethylsulfonyl-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl] picoline. The amide was obtained in 99.2% yield.
1 H-NMR (DMSO-d 6 ) δ: 11.55 (1H, brs), 10.45 (1H, s), 8.65 (1H, s), 8.38 (1H, d), 7. 96 (1H, d), 7.57 (1H, d), 7.26 (1H, d), 3.84 (2H, q), 1.32 (3H, t).

実施例１９

Figure 2016027019
窒素雰囲気下で、３−エチルスルホニル−６−クロロ−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルフィニル）フェニル］ピコリンアミド１．００ｇ、ｐ−トルエンスルホン酸一水和物０．７４ｇ及びクロロベンゼン５．２１ｇの混合物を、１４０℃で８時間還流脱水した。室温まで放冷した混合物を飽和炭酸水素ナトリウム水溶液に加え、分液したのち、有機層を濃縮することにより、２−（６−クロロ−３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルフィニル）ベンズオキサゾールを０．９５ｇ得た。
1Ｈ−ＮＭＲ（ＣＤＣｌ3）δ：８．５３（１Ｈ，ｄ），８．３６（１Ｈ，ｄ），７．９４（１Ｈ，ｄｄ），７．８９（１Ｈ，ｄｄ），７．７６（１Ｈ，ｄ），４．０１（２Ｈ，ｑ），１．４４（３Ｈ，ｔ）． Example 19
Figure 2016027019
Under a nitrogen atmosphere, 1.00 g of 3-ethylsulfonyl-6-chloro-N- [2-hydroxy-5- (trifluoromethylsulfinyl) phenyl] picolinamide, 0.74 g of p-toluenesulfonic acid monohydrate and A mixture of 5.21 g of chlorobenzene was reflux-dehydrated at 140 ° C. for 8 hours. The mixture allowed to cool to room temperature was added to a saturated aqueous sodium hydrogen carbonate solution, and the mixture was partitioned. The organic layer was concentrated to give 2- (6-chloro-3-ethylsulfonylpyridin-2-yl) -5- (tri 0.95 g of (fluoromethylsulfinyl) benzoxazole was obtained.
1 H-NMR (CDCl 3 ) δ: 8.53 (1H, d), 8.36 (1H, d), 7.94 (1H, dd), 7.89 (1H, dd), 7.76 ( 1H, d), 4.01 (2H, q), 1.44 (3H, t).

実施例２０

Figure 2016027019
窒素雰囲気下で、２−アミノ−４−（トリフルオロメチルスルホニル）フェノール４．５８ｇ及びテトラヒドロフラン３６．８２ｇを混合し、０℃に冷却したのち、（３−エチルスルホニル）−６−クロロ−２−ピリジンカルボン酸クロリド５．３０ｇとテトラヒドロフラン１０．６０ｇとの混合物を１時間かけて滴下し、０℃で４時間攪拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出し、有機層を減圧下濃縮することにより、３−エチルスルホニル−６−クロロ−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルホニル）フェニル］ピコリンアミドを収率９８．４％で得た。
1Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ6）δ：１０．７７（１Ｈ，ｂｒｓ），９．９７（１Ｈ，ｓ），９．０９（１Ｈ，ｓ），８．４９（１Ｈ，ｄ），７．８５（１Ｈ，ｄ），７．７７（１Ｈ，ｄ），７．１８（１Ｈ，ｄ），３．８０（２Ｈ，ｑ），１．２２（３Ｈ，ｔ）． Example 20
Figure 2016027019
Under a nitrogen atmosphere, 4.58 g of 2-amino-4- (trifluoromethylsulfonyl) phenol and 36.82 g of tetrahydrofuran were mixed, cooled to 0 ° C., and then (3-ethylsulfonyl) -6-chloro-2- A mixture of 5.30 g of pyridinecarboxylic acid chloride and 10.60 g of tetrahydrofuran was added dropwise over 1 hour, and the mixture was stirred at 0 ° C. for 4 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated under reduced pressure to give 3-ethylsulfonyl-6-chloro-N- [2-hydroxy-5- (trifluoromethylsulfonyl). ) Phenyl] picolinamide was obtained in 98.4% yield.
1 H-NMR (DMSO-d 6 ) δ: 10.77 (1H, brs), 9.97 (1H, s), 9.09 (1H, s), 8.49 (1H, d), 7. 85 (1H, d), 7.77 (1H, d), 7.18 (1H, d), 3.80 (2H, q), 1.22 (3H, t).

実施例２１

Figure 2016027019
窒素雰囲気下で、３−エチルスルホニル−６−クロロ−Ｎ−［２−ヒドロキシ−５−（トリフルオロメチルスルホニル）フェニル］ピコリンアミド１．０１ｇ、ｐ−トルエンスルホン酸一水和物０．７２ｇ及びクロロベンゼン５．３２ｇの混合物を、１４０℃で８時間還流脱水した。室温まで放冷した混合物を飽和炭酸水素ナトリウム水溶液に加え、分液したのち、有機層を濃縮することにより、２−（６−クロロ−３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルホニル）ベンズオキサゾールを０．９５ｇ得た。
1Ｈ−ＮＭＲ（ＣＤＣｌ3）δ：８．５９（１Ｈ，ｄ），８．５４（１Ｈ，ｄ），８．１８（１Ｈ，ｄｄ），７．９８（１Ｈ，ｄ），７．７９（１Ｈ，ｄ），３．９８（２Ｈ，ｑ），１．４５（３Ｈ，ｔ）． Example 21
Figure 2016027019
Under a nitrogen atmosphere, 1.01 g of 3-ethylsulfonyl-6-chloro-N- [2-hydroxy-5- (trifluoromethylsulfonyl) phenyl] picolinamide, 0.72 g of p-toluenesulfonic acid monohydrate and A mixture of 5.32 g of chlorobenzene was dehydrated under reflux at 140 ° C. for 8 hours. The mixture allowed to cool to room temperature was added to a saturated aqueous sodium hydrogen carbonate solution, and the mixture was partitioned. The organic layer was concentrated to give 2- (6-chloro-3-ethylsulfonylpyridin-2-yl) -5- (tri 0.95 g of fluoromethylsulfonyl) benzoxazole was obtained.
1 H-NMR (CDCl 3 ) δ: 8.59 (1H, d), 8.54 (1H, d), 8.18 (1H, dd), 7.98 (1H, d), 7.79 ( 1H, d), 3.98 (2H, q), 1.45 (3H, t).

実施例２２

Figure 2016027019
窒素雰囲気下で、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルフィニル）ベンズオキサゾールと、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルフィニル）ベンズオキサゾールに対して１モル当量のｐ−トルエンスルホン酸一水和物とキシレンとを混合して３０分間撹拌し、得られた混合物を濃縮することにより、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルフィニル）ベンズオキサゾール・ｐ−トルエンスルホン酸塩が得られる。 Example 22
Figure 2016027019
Under a nitrogen atmosphere, 2- (3-ethylsulfonylpyridin-2-yl) -5- (trifluoromethylsulfinyl) benzoxazole and 2- (3-ethylsulfonylpyridin-2-yl) -5- (trifluoro Methylsulfinyl) benzoxazole is mixed with 1 molar equivalent of p-toluenesulfonic acid monohydrate and xylene and stirred for 30 minutes, and the resulting mixture is concentrated to give 2- (3-ethylsulfonyl). Pyridin-2-yl) -5- (trifluoromethylsulfinyl) benzoxazole.p-toluenesulfonate is obtained.

実施例２３
ｐ−トルエンスルホン酸一水和物の代わりに、塩酸、臭化水素酸、ヨウ化水素酸、ベンゼンスルホン酸、メタンスルホン酸、又はカンファースルホン酸を用い、実施例２２に記載の方法と同様の方法により、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルフィニル）ベンズオキサゾールの酸付加塩を得ることができる。 Example 23
In place of p-toluenesulfonic acid monohydrate, hydrochloric acid, hydrobromic acid, hydroiodic acid, benzenesulfonic acid, methanesulfonic acid, or camphorsulfonic acid was used, and the same method as described in Example 22 was used. By the method, an acid addition salt of 2- (3-ethylsulfonylpyridin-2-yl) -5- (trifluoromethylsulfinyl) benzoxazole can be obtained.

実施例２４

Figure 2016027019
窒素雰囲気下で、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルホニル）ベンズオキサゾールと、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルホニル）ベンズオキサゾールに対して１モル当量のｐ−トルエンスルホン酸一水和物とキシレンとを混合して３０分間撹拌し、得られた混合物を濃縮することにより、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルホニル）ベンズオキサゾール・ｐ−トルエンスルホン酸塩が得られる。 Example 24
Figure 2016027019
Under a nitrogen atmosphere, 2- (3-ethylsulfonylpyridin-2-yl) -5- (trifluoromethylsulfonyl) benzoxazole and 2- (3-ethylsulfonylpyridin-2-yl) -5- (trifluoro Methylsulfonyl) benzoxazole is mixed with 1 molar equivalent of p-toluenesulfonic acid monohydrate and xylene and stirred for 30 minutes, and the resulting mixture is concentrated to give 2- (3-ethylsulfonyl). Pyridin-2-yl) -5- (trifluoromethylsulfonyl) benzoxazole.p-toluenesulfonate is obtained.

実施例２５
ｐ−トルエンスルホン酸一水和物の代わりに、塩酸、臭化水素酸、ヨウ化水素酸、ベンゼンスルホン酸、メタンスルホン酸、又はカンファースルホン酸を用い、実施例２４に記載の方法と同様の方法により、２−（３−エチルスルホニルピリジン−２−イル）−５−（トリフルオロメチルスルホニル）ベンズオキサゾールの酸付加塩を得ることができる。 Example 25
In place of p-toluenesulfonic acid monohydrate, hydrochloric acid, hydrobromic acid, hydroiodic acid, benzenesulfonic acid, methanesulfonic acid, or camphorsulfonic acid was used, and the same method as described in Example 24 was used. By the method, an acid addition salt of 2- (3-ethylsulfonylpyridin-2-yl) -5- (trifluoromethylsulfonyl) benzoxazole can be obtained.

比較例１

Figure 2016027019
窒素雰囲気下で、（３−エチルスルホニル）−２−ピリジンカルボン酸３．００ｇ、トルエン９．００ｇ及びＮ，Ｎ−ジメチルホルムアミド０．１１ｇを混合し、６０℃に加熱したのち塩化チオニル２．０３ｇを５時間かけて滴下し、６０℃で４時間攪拌した。反応液にｎ−ブタノールを加え、高速液体クロマトグラフィーを用いて分析したところ、（３−エチルスルホニル）−２−ピリジンカルボン酸クロリドを収率６５．３％で得た。 Comparative Example 1
Figure 2016027019
Under a nitrogen atmosphere, 3.00 g of (3-ethylsulfonyl) -2-pyridinecarboxylic acid, 9.00 g of toluene and 0.11 g of N, N-dimethylformamide were mixed, heated to 60 ° C., and 2.03 g of thionyl chloride. Was added dropwise over 5 hours and stirred at 60 ° C. for 4 hours. When n-butanol was added to the reaction solution and analyzed using high performance liquid chromatography, (3-ethylsulfonyl) -2-pyridinecarboxylic acid chloride was obtained in a yield of 65.3%.

本発明により、有害生物に対して優れた防除効力を有する式（４）で表される化合物を製造することができる。   According to the present invention, a compound represented by the formula (4) having an excellent control effect against pests can be produced.

Claims (7)

式（２）
Figure 2016027019
［式中、Ｒ1はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、
Ｒはそれぞれ独立して、ハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基、又はハロゲン原子を表し、ｎは０、１、２または３を表し、Ｍはナトリウム、カリウム、又はリチウムを表す］で表される化合物と、塩化チオニルとを反応させて、式（１）
Figure 2016027019
［式中、Ｒ1、Ｒおよびｎは前記と同じ意味を表す。］
で表される化合物を得る工程Ａ；及び
式（１）で表される化合物と式（５）
Figure 2016027019
［式中、Ａ1は窒素原子又は＝ＣＨ−を表し、
Ｒ5はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、ｍは１または２を表す］
で表される化合物とを反応させることにより、式（３）
Figure 2016027019
［式中、Ｒ1、Ｒ、Ｒ5、Ａ1、ｍおよびｎは、前記と同じ意味を表す。］
で表される化合物またはその酸塩を製造する工程Ｂ；及び
式（３）で表される化合物またはその酸塩を、酸の存在下で１００℃〜１８０℃で環化することにより、式（４）
Figure 2016027019
［式中、Ｒ1、Ｒ、Ｒ5、Ａ1、ｍおよびｎは、前記と同じ意味を表す。］
で表される化合物を得る工程Ｃ；を含む、式（４）で表される化合物の製造方法。 Formula (2)
Figure 2016027019
[In the formula, R 1 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom. Represent,
R independently represents a C 1-6 chain hydrocarbon group which may have a halogen atom, or a halogen atom, n represents 0, 1, 2 or 3, M represents sodium, A compound represented by formula (1) is reacted with thionyl chloride.
Figure 2016027019
[Wherein R 1 , R and n represent the same meaning as described above. ]
Step A to obtain a compound represented by formula: and a compound represented by formula (1) and formula (5)
Figure 2016027019
[In the formula, A1 represents a nitrogen atom or = CH-;
R 5 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom; Represents 1 or 2]
Is reacted with a compound represented by the formula (3)
Figure 2016027019
[Wherein, R 1 , R, R 5 , A 1 , m and n represent the same meaning as described above. ]
Step B for producing a compound represented by the formula (I) or an acid salt thereof; and cyclization of the compound represented by the formula (3) or the acid salt thereof at 100 ° C. to 180 ° C. in the presence of an acid, 4)
Figure 2016027019
[Wherein, R 1 , R, R 5 , A 1 , m and n represent the same meaning as described above. ]
A process for producing a compound represented by the formula (4), comprising a step C of obtaining a compound represented by the formula: 工程Ｃにおける酸が、スルホン酸化合物である、請求項１に記載の製造方法。 The manufacturing method of Claim 1 whose acid in the process C is a sulfonic acid compound. 工程Ｃにおける酸が、ｐ−トルエンスルホン酸である、請求項１に記載の製造方法。 The production method according to claim 1, wherein the acid in Step C is p-toluenesulfonic acid. 工程Ｃにおける酸が、メタンスルホン酸である、請求項１に記載の製造方法。 The production method according to claim 1, wherein the acid in Step C is methanesulfonic acid. 式（２）
Figure 2016027019
［式中、Ｒ1はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、
Ｒはそれぞれ独立して、ハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基、又はハロゲン原子を表し、ｎは０、１、２または３を表し、Ｍはナトリウム、カリウム、又はリチウムを表す］で表される化合物と、塩化チオニルとを反応させて、式（１）
Figure 2016027019
［式中、Ｒ1、Ｒおよびｎは前記と同じ意味を表す。］
で表される化合物を得る工程Ａ；及び
式（１）で表される化合物と式（５）
Figure 2016027019
［式中、Ａ1は窒素原子又は＝ＣＨ−を表し、
Ｒ5はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、ｍは１または２を表す］
で表される化合物とを反応させることにより、式（３）
Figure 2016027019
［式中、Ｒ1、Ｒ、Ｒ5、Ａ1、ｍおよびｎは、前記と同じ意味を表す。］
で表される化合物を製造する工程Ｂ；を含む、式（３）で表される化合物またはその酸塩の製造方法。 Formula (2)
Figure 2016027019
[In the formula, R 1 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom. Represent,
R independently represents a C 1-6 chain hydrocarbon group which may have a halogen atom, or a halogen atom, n represents 0, 1, 2 or 3, M represents sodium, A compound represented by formula (1) is reacted with thionyl chloride.
Figure 2016027019
[Wherein R 1 , R and n represent the same meaning as described above. ]
Step A to obtain a compound represented by formula: and a compound represented by formula (1) and formula (5)
Figure 2016027019
[Wherein A 1 represents a nitrogen atom or ═CH—,
R 5 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom; Represents 1 or 2]
Is reacted with a compound represented by the formula (3)
Figure 2016027019
[Wherein, R 1 , R, R 5 , A 1 , m and n represent the same meaning as described above. ]
A process for producing a compound represented by formula (3) or a salt thereof: 工程Ｂにおいて、用いる溶媒がエーテル溶媒を含む、請求項１〜５いずれかに記載の製造方法。 The manufacturing method in any one of Claims 1-5 in which the solvent used in the process B contains an ether solvent. 式（２）
Figure 2016027019
［式中、Ｒ1はハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基又はハロゲン原子を有していてもよい炭素数３〜６の脂環式炭化水素基を表し、
Ｒはそれぞれ独立して、ハロゲン原子を有していてもよい炭素数１〜６の鎖式炭化水素基、又はハロゲン原子を表し、ｎは０、１、２または３を表し、Ｍはナトリウム、カリウム、又はリチウムを表す］で表される化合物と、塩化チオニルとを反応させて、式（１）
Figure 2016027019
［式中、Ｒ1、Ｒ及びｎは前記と同じ意味を表す。］
で表される化合物を得る工程Ａ；を含む、式（１）で表される化合物の製造方法。 Formula (2)
Figure 2016027019
[In the formula, R 1 represents a C 1-6 chain hydrocarbon group which may have a halogen atom or a C 3-6 alicyclic hydrocarbon group which may have a halogen atom. Represent,
R independently represents a C 1-6 chain hydrocarbon group which may have a halogen atom, or a halogen atom, n represents 0, 1, 2 or 3, M represents sodium, A compound represented by formula (1) is reacted with thionyl chloride.
Figure 2016027019
[Wherein R 1 , R and n represent the same meaning as described above. ]
A process for producing a compound represented by the formula (1), which comprises the step A of obtaining a compound represented by the formula:
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